The Role of Cytokines in Traumatic Brain Injury

Traumatic brain injury (TBI) is a major cause of death and disability, mainly in persons under 45 years of age and it remains clinically challenging due to its heterogeneous pathophysiology and unpredictable course. Except from the initial mechanical damage, secondary injury -largely driven by neuroinflammation-plays a critical role in outcome and extent of recovery. Cytokines are central mediators of this immune response and have therefore been extensively studied as potential biomarkers for TBI diagnosis, need of imaging and prognosis. Among pro-inflammatory cytokines, IL-1β is rapidly upregulated after TBI and contributes to blood-brain barrier disruption and secondary damage. Furthermore, experimental studies suggest that IL-1 inhibition could be neuroprotective. IL-6 is up to date the most extensively studied cytokine and shows strong associations with injury severity, neuroimaging abnormalities, mortality and long-term functional outcomes across multiple adult and pediatric studies. Nevertheless, results vary depending on the biological compartment and timing. Anti-inflammatory IL-10 levels correlate with injury severity and has shown promise in distinguishing CT-positive from CT-negative mild TBI patients, potentially reducing unnecessary imaging, though findings are inconsistent. Other cytokines, including IL-17, TNF-α, IL-8, IL-9, and IL-15, have been correlated to post-traumatic neuroinflammation and may have diagnostic or prognostic value. Overall, IL-6 and IL-10 currently appear to be the most promising cytokine as biomarkers, however future research should focus on standardized cytokines assessment methods and possible use of multimarker panels.